Clinical Significances Of TS, TP And PCNA Expression In Cervical Carcinoma Tissue

Background and Objective: The incidence rate of cervical carcinoma is ranked the first among women's malignancy in our country. Cervical carcinoma has the features of high malignancy, metastatic and recurring tendency, and is a threat for women's health. Therefore, looking for a new approach from genie level for the cure of cervical cancer is becoming one of the focuses in cervical carcinoma research. Nowadays the treatments for cervical carcinoma are mainly concentrated on operation and radiotherapy. Although these methods have got some success, a part of the patients didn't get control or relapsed after primary treatment due to the inefficiency of regional healing. Therefore, it is an important subject to look for a new method that can effectively detect and cure cervical carcinoma in its early stage or block its metastasis and relapse.Thymidylate synthase (TS) and thymidine phosphorylase (TP) are two key enzymes involved in pyrimidine metabolism and DNA synthesis. Thymidylate synthase (TS) catalyzes the reductive methylation of dUMP to generate thymidylate, which was the key step for de novo DNA biosynthesis. The high expression of TS was associated with abnormal cell proliferating, apoptosis regression and resisting to chematherapy. Thymidine phosphorylase (TP) catalyzes the reversible phosphorolysis of thymidine,deoxyuridine and their analogs to their respective bases and 2-deoxyribose-1-phosphate. It also catalyzes deoxyribosyl transfer from one deoxynucleoside to another base to form a second nucleoside. It is identical with platelet-derived endothelial cell growth factor (PD-ECGF), having angiogenic activity in vivo and playing an important role in tumor growth, invasion and metastasis. This experiment is designed to explore the expressions of TS, TP and proliferating cell nuclear antigen (PCNA) in cervical intraepithelial neoplasia and cervical carcinoma and to establish their significances in order to provide new direction and proof for early clinical diagnosis and treatment to cervical carcinoma.Materials and methods: 85 cases of paraffin embeded tissue specimens were collected, which contain 33 cases of cervical carcinoma, 42 cases of cervical intraepithelial neoplasia (13 cases of CIN â…  , 8 cases of CINâ…¡ and 21 cases of CINâ…¢) and 10 cases of chronic cervical inflammation. They were all confirmed pathologically. S-P immunohistochemistry technique was used to detect the expressions of TS, TP and PCNA proteins in chronic cervical inflammation, cervical intraepithelial neoplasia and cervical carcinoma tissue.Results:1. There was no positive expression of TS in chronic cervical inflammation. The positive expression rate of TS in cervical carcinoma and CIN was 51.5%, 45.2%, respectively, which were all significantly higher than that in chronic cervical inflammation (P=0.006 and 0.004). There was no difference of TS positive rate between in cervical carcinoma and in CIN. In the group of cervical cancer, the positive rate of TS in stage â…  and stage â…¡ was 25%, 65%, respectively. There was significant difference between the two groups (P=0.033). In the group with lymph node metastasis and the group without lymph node metastasis, the positive rate of TS was 87.5%, 36%, respectively. There was significant difference between the two groups (P=0.015). But there was no significant difference of TS positive expression rate when compared with each other in different histological grades and in different invasive depth (P=0.343 and0.350).2. There was no positive expression of TP in chronic cervical inflammation. The positive expression rate of TP in cervical carcinoma and CIN was 69.7%, 35.7%, respectively, which were all significantly higher than that in chronic cervical inflammation (P=0.000 and 0.022). The positive expression rate of TP in cervical carcinoma was also significantly higher than that in CIN (P=0.003). In the group of cervical cancer, the positive rate of TP in stage I and stage II was 41.7%, 85%, respectively. There was significant difference between the two groups (P=0.018). In the group with lymph node metastasis and the group without lymph node metastasis, the positive rate of TP was 100%, 60%, respectively. There was significant difference between the two groups (P=0.035). In the group of deep muscular layer invasion and the group of superficial muscular layer invasion, the positive rate of TP was 85%, 40%, respectively. There was significant difference between the two groups (P=0.018). But there was no significant difference of TP positive expression rate when compared with each other in different histological grades (P=0.681).3. The positive expression rate of PCNA in chronic cervical inflammation, CIN and cervical carcinoma was 20%, 64.3% and 100%, respectively. The positive expression rates of PCNA in CIN and cervical carcinoma were all significantly higher than that in chronic cervical inflammation (P=0.029 and 0.000). It was also significantly higher in cervical carcinoma than in CIN (P=0.000).4. In 75 CIN and cervical carcinoma samples, 33 cases were positive expression of both TS and PCNA, while 13 cases were negative expression of both TS and PCNA. There exists an association between TS and PCNA expression. (Pearson p=0.3169, x 2=8.371,P<0.005).Conclusion:1. The positive rates of TS, TP and PCNA in cervical intraepithelial neoplasia and cervical carcinoma were all significantly higher than that in chronic cervical inflammation, which indicated that they all participate in the whole stage of cervicallesion progression and it might be the early event. It is suggested that the positive expressions of TS, TP and PCNA might be of value in guiding early clinical dignosis and prevention and cure.2. The positive rates of TS and TP were all correlated with clinical stage and lymph node metastasis in cervical carcinoma, which indicated that both of them might play important roles in the metastasis of cervical carcinoma. It is suggested that the positive expressions of TS and TP might be of value in guiding treatment and judging prognosis for cervical carcinoma.3. The expression of TS was positively related to the expression of PCNA, and the positive rate of PCNA in cervical carcinoma was 100%, indicating that there was cell over-proliferating in the process of cervical oncogenesis and TS might participate in it, which have some significances in revealing the mechanism of cervical oncogenesis.